Phase I Trial of 225Ac-J591 in Patients With mCRPC

NCT03276572 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 17060182817R01CA207645-03
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, single-center Phase I dose escalation study designed to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of 225Ac-J591 in a single dose regimen.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Subjects With Dose Limiting Toxicities (DLT)

  Count of participants will be measured by the recommended phase II dose in utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for DLTs.

  Assessed from start of treatment to up to 8 weeks after first study drug administration.

• Number of Subjects Who Reached Maximum Tolerated Dose (MTD)

  The MTD is the highest dose amongst the different dose-level cohorts in this study at which no more than 2 (33%) of the subjects in a cohort experience DLT.

  Assessed from start of treatment to up to 8 weeks after first study drug administration.

Secondary Outcomes (4)

• Number of Subjects With Prostate Specific Antigen (PSA) Response

  PSA was assessed at screening, and up to 6 months after first treatment with study drug.

• Number of Subjects With Circulating Tumor Cells (CTC) Response

  CTC was assessed at screening and 12 weeks after starting study drug.

• Number of Subjects With Radiographic (Imaging) Response

  Response were assessed for patients throughout their duration on the study, up to 3 years.

• Progression Free Survival (PFS)

  From the start of treatment to progression, up to 3 years

Study Arms (1)

All Subjects

EXPERIMENTAL

A single dose of 225Ac-J591 will be given to subjects with documented progressive metastatic CRPC.

Drug: 225Ac-J591

Interventions

225Ac-J591 DRUG

225Ac-J591 (13.3 KBq/Kg - 93.3 KBq/Kg or 0.36 uCi/Kg - 2.52 uCi/Kg) on day 1

Also known as: 68Ga-PSMA-HBED-CC injection for PET/CT Scan on day 1 and at end of study

All Subjects

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Adult male patients of \>18 years age with documented progressive metastatic CRPC
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of prostate
• Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria:
• PSA progression
• Objective radiographic progression in soft tissue
• New bone lesions
• ECOG performance status of 0-2
• Have serum testosterone \< 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH analogue (agonist/antagonist) if they have not undergone bilateral orchiectomy.
• Have previously been treated with at least one of the following:
• Androgen receptor signaling inhibitor (such as enzalutamide)
• CYP 17 inhibitor (such as abiraterone acetate)
• Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.
• Age \> 18 years
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count \>2,000 cells/mm3
• Hemoglobin ≥9 g/dL

You may not qualify if:

• Implantation of investigational medical device ≤4 weeks of Cycle 1, Day 1 or current enrollment in oncologic investigational drug or device study
• Use of investigational drugs ≤4 weeks or \<5 half-lives of Cycle 1, Day 1 or current enrollment in investigational oncology drug or device study
• Prior systemic beta-emitting bone-seeking radioisotopes
• Known active brain metastases or leptomeningeal disease
• History of deep vein thrombosis and/or pulmonary embolus within 1 month of C1D1
• Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
• Radiation therapy for treatment of PC ≤4 weeks of Day 1 Cycle 1
• Patients on stable dose of bisphosphonates or Denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/Denosumab therapy during the DLT-assessment period of the study.
• Having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principle investigator and chairperson during the study and for 1 month after last study drug administration
• Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse.
• Known history of known myelodysplastic syndrome

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Prostate Cancer Foundation: collaborator
• United States Department of Defense: collaborator
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Tulane Cancer Center Clinic

New Orleans, Louisiana, 70112, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Related Publications (2)

• Tagawa ST, Thomas C, Sartor AO, Sun M, Stangl-Kremser J, Bissassar M, Vallabhajosula S, Huicochea Castellanos S, Nauseef JT, Sternberg CN, Molina A, Ballman K, Nanus DM, Osborne JR, Bander NH. Prostate-Specific Membrane Antigen-Targeting Alpha Emitter via Antibody Delivery for Metastatic Castration-Resistant Prostate Cancer: A Phase I Dose-Escalation Study of 225Ac-J591. J Clin Oncol. 2024 Mar 1;42(7):842-851. doi: 10.1200/JCO.23.00573. Epub 2023 Nov 3.

  PMID: 37922438 DERIVED

• Vlachostergios PJ, Niaz MJ, Skafida M, Mosallaie SA, Thomas C, Christos PJ, Osborne JR, Molina AM, Nanus DM, Bander NH, Tagawa ST. Imaging expression of prostate-specific membrane antigen and response to PSMA-targeted beta-emitting radionuclide therapies in metastatic castration-resistant prostate cancer. Prostate. 2021 Apr;81(5):279-285. doi: 10.1002/pros.24104. Epub 2021 Jan 19.

  PMID: 33465252 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

gallium 68 PSMA-11

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Dr. Scott Tagawa
• Organization: Weill Cornell Medicine

stt2007@med.cornell.edu

646-962-2027

Study Officials

• Scott Tagawa, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: September 8, 2017
• Study Start: October 10, 2017
• Primary Completion: January 7, 2021
• Study Completion: September 1, 2023
• Last Updated: June 13, 2024
• Results First Posted: December 6, 2022

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)